Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms.

ABSTRACT: The mechanistic target of rapamycin complex 1 (mTORC1) growth pathway detects nutrients through a variety of sensors and regulators that converge on the Rag GTPases, which form heterodimers consisting of RagA or RagB tightly bound to RagC or RagD and control the subcellular localization of mTORC1. The Rag heterodimer uses a unique "locking" mechanism to stabilize its active (^GTPRagA-RagC^GDP) or inactive (^GDPRagA-RagC^GTP) nucleotide states. The Ragulator complex tethers the Rag heterodimer to the lysosomal surface, and the SLC38A9 transmembrane protein is a lysosomal arginine sensor that upon activation stimulates mTORC1 activity through the Rag GTPases. How Ragulator and SLC38A9 control the nucleotide loading state of the Rag GTPases remains inco

SUBMITTER: Shen K 

PROVIDER: S-EPMC6156610 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature